NM_198834.3:c.3246+2965G>A

Variant names:

• chr17-37232010-C-T
• rs2680398
• NM_198834.3:c.3246+2965G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198834.3(ACACA):​c.3246+2965G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,130 control chromosomes in the GnomAD database, including 1,314 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1314 hom., cov: 32)
• Consequence: ACACA NM_198834.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 10 publications found

Genes affected

ACACA (HGNC:84): (acetyl-CoA carboxylase alpha) Acetyl-CoA carboxylase (ACC) is a complex multifunctional enzyme system. ACC is a biotin-containing enzyme which catalyzes the carboxylation of acetyl-CoA to malonyl-CoA, the rate-limiting step in fatty acid synthesis. There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The enzyme is under long term control at the transcriptional and translational levels and under short term regulation by the phosphorylation/dephosphorylation of targeted serine residues and by allosteric transformation by citrate or palmitoyl-CoA. Multiple alternatively spliced transcript variants divergent in the 5' sequence and encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACACA Gene-Disease associations (from GenCC):

• acetyl-coa carboxylase deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198834.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	NM_198834.3	MANE Select	c.3246+2965G>A		intron	N/A	NP_942131.1
	ACACA	NM_198836.3		c.3135+2965G>A		intron	N/A	NP_942133.1
	ACACA	NM_198839.3		c.3135+2965G>A		intron	N/A	NP_942136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACACA	ENST00000616317.5	TSL:1 MANE Select	c.3246+2965G>A		intron	N/A	ENSP00000483300.1
	ACACA	ENST00000614428.4	TSL:1	c.3135+2965G>A		intron	N/A	ENSP00000478547.1
	ACACA	ENST00000613146.4	TSL:1	n.3331+2965G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16754 AN: 152012 Hom.: 1313 Cov.: 32

Gnomad AFR AF: 0.0325

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16754 AN: 152130 Hom.: 1314 Cov.: 32 AF XY: 0.117 AC XY: 8676 AN XY: 74364

African (AFR) AF: 0.0325 AC: 1349 AN: 41538

American (AMR) AF: 0.138 AC: 2109 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 414 AN: 3464

East Asian (EAS) AF: 0.359 AC: 1858 AN: 5174

South Asian (SAS) AF: 0.205 AC: 988 AN: 4810

European-Finnish (FIN) AF: 0.180 AC: 1898 AN: 10566

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7810 AN: 67994

Other (OTH) AF: 0.111 AC: 234 AN: 2110

Alfa AF: 0.110 Hom.: 2266

Bravo AF: 0.103

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2680398; hg19: chr17-35588925;